title: Sigmoid Th17 populations, the HIV latent reservoir, and microbial translocation in men on long-term antiretroviral therapy.
abstract: OBJECTIVE
  Th17 cells play an important role in mucosal defence and repair and are highly susceptible to infection by HIV. Antiretroviral therapy (ART) suppresses HIV viremia and can restore CD4(+) numbers in the blood and gastrointestinal mucosa, but the resolution of systemic inflammation and gut microbial translocation is often incomplete. We hypothesized that this might relate to persistent dysregulation of gut CD4(+) Th17 subsets.
  
  
  METHODS
  Blood and sigmoid biopsies were collected from HIV-uninfected men, chronically HIV-infected, ART-naive men, and men on effective ART for more than 4 years. Sigmoid provirus levels were assayed blind to participant status, as were CD4(+) Th17 subsets, systemic markers of microbial translocation, and cellular immune activation.
  
  
  RESULTS
  There was minimal CD4(+) Th17 dysregulation in the blood until later stage HIV infection, but gastrointestinal Th17 depletion was apparent much earlier, along with increased plasma markers of microbial translocation. Plasma lipopolysaccharide (LPS) remained elevated despite overall normalization of sigmoid Th17 populations on long-term ART, although there was considerable interindividual variability in Th17 reconstitution. An inverse correlation was observed between plasma LPS levels and gut Th17 frequencies, and higher plasma LPS levels correlated with an increased gut HIV proviral reservoir.
  
  
  CONCLUSIONS
  Sigmoid Th17 populations were preferentially depleted during HIV infection. Despite overall CD4(+) T-cell reconstitution, sigmoid Th17 frequencies after long-term ART were heterogeneous and higher frequencies were correlated with reduced microbial translocation.
authors.affiliation: Department of Medicine, University of Toronto, Canada.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chege
authors.forename: Prameet M
authors.initials: PM
authors.lastname: Sheth
authors.forename: Taylor
authors.initials: T
authors.lastname: Kain
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Mona
authors.initials: M
authors.lastname: Loutfy
authors.forename: Roberta
authors.initials: R
authors.lastname: Halpenny
authors.forename: Gabor
authors.initials: G
authors.lastname: Kandel
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D000818:Animals; D018988:Bacterial Translocation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D012809:Colon, Sigmoid / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity; D058504:Th17 Cells / Q000276:immunology*